Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov



## Zinc, Zinc Salts and Zeolites Amended Final Work Plan Registration Review

Case Number: 4099

Approved By:

Acting Director, Antimicrobials Division

Da t e: 

# /Z- tjf l'LDocket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

2 Zinc, Zinc Salts and Zeolites AMENDED FINAL WORK PLAN

Introduction

This document amends the Final Work Plan (FWP) for the registration review of Zinc, Zinc
Salts and Zeolites

. Since the publicat i on of the September 2009 Final Work Plan, the Agency has
reviewed the data requirements previously identified to support the registration r e view of Case 4099 (Zinc, Zinc Salts and Zeolites). Th is document amends the September 2009 FWP to clarify the requirements and remove the following studi es which will no longer be required to support
the risk assessment:

• 835.1110: Activated Sludge Sorption Isotherm

• 835.1240: Leaching and adsorption/desorption

• 835.2240: Photodegradation in water

• 835.2410: Photodegradation in soil

• 835.4100: Aerobic soil metabolism

• 835.4400: Anaerobic aquatic metabolism

• 870.3100 1 : 90-day Oral Toxicity-rodent

• 870.3150 1 : 90-day Oral Toxicity-non-rodent

• 870.3250 1 : 90-day Dermal- rodent

• 870.3700 1 : Developmental Toxicity-rodent

• 870.3800 1 : Reproductive Toxicity- rodent

Unless otherwise stated by the Agency, all other elements of the Agency's September 2009 Zinc,
Zinc Salts and Zeolites FWP remain unchanged.

Summary of Data Requirements Summary tables of the data requi red to support the registration revi ew of each of the five active ingredients in the Zinc, Zinc Salts and Zeolites Case (Zinc chloride (PC Code 087801), Zinc oxide (PC Code 088502), Zinc sulfate (PC C ode 089001), Zinc (PC Code 129015), and Zinc sulfate monohydrate (PC Code 527200)) are presented below.

1 These studies are no longer needed for risk assessment because information to assess potential risk to zeolite compounds will be submitted in response to the silver zeolite DCI anticipated to be issued as part of the Silver Compounds registration review (Case 4082 and Case 5015).Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

3 Data Requirements for the Registration Review of Zinc Oxide (PC Code 088502 )

Guideline
Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI receipt)
850.3300 or
OECD 209 2,3,4 Activated Sludge Respiration Inhibition TGAI 12

835.1230 2 Sediment and soil adsorption/desorption TGAI 12

850.4100 3,5,6,7 Seedling emergence, Tier II TGAI 12

850.4250 5,6 Vegetative vigor dose response test using rice ( Oryza sativa ) TGAI 12

850.4400 2,3,4,6 Aquatic plant growth using floating macrophyte Lemna gibba TGAI 12

850.4500 2,3,6,8 Aquatic Plant Growth (green alga, freshwater diatom, saltwater diatom) TGAI 12

850.4550 2,3,6,9 Aquatic Plant Growth (cyanobacteria) TGAI 12

SS 5,10 Aquatic Leaching from Wood TGAI 24

SS 5,11 Soil Leaching from Wood TGAI 24

2 Study is required to support the registration review of wood preservative uses, material preservative uses, and
outdoor moss control uses.

3 Analytical measurements of zinc (total, dissolved, an d free) and the following water quality parameters that are critical to metal speciation in solution are required: temper ature, pH, dissolved organic carbon (distribution of humic and fulvic acids), major cation (Ca, Mg, Na and K), major anions (SO 4 and Cl), alkalinity, and sulfide content.

4 Because applied zinc and zinc salts will react in aqueous solutions to form free zinc ion and dissolved complexes, the Agency recognizes there is potential for tests conducted with one zinc active ingredient to potentially bridge to another. However, the Agency also recognizes that the content and formation of the free zinc ion and complexes in a test can be affected by dissolution and reaction kinetics and therefore data generated for on e of the more soluble zinc active ingredient forms is recommended for use in such bridging.

5 Study is required to support the registration review of wood preservative uses.

6 Results from a tier II study are required to be submitted to satisfy this requirement.

7 Seedling emergence was presented in the Final Work Pl an as 850.4225; however, test guidelines 850.4100 and 850.4225 were merged and harmonized into OCSPP 850.4100 in a Federal Register Notice dated June 27, 2012 (FRL-9333-1).

8 Results for three species ( Selenastrum capricornutum (green alga), one freshwate r diatom, and one saltwater diatom) are required to fulfill requirement. If the NOAE C of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

9 Results for one species of cyanobacteria are required to fu lfill requirement. If the NOAEC of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

10 For guidance, please refer to: Standard Method of Dete rmining the Leachability of Wood Preservatives, American Wood Preservers’ Association (AWPA) Standard E11-06 or E11-12.

11 For guidance, please refer to: Standard Method of Dete rmining the Leachability of Wood Preservatives in Soil Contact, American Wood Preservers’ Association (AWPA) Standard E20-06 or E20-08.Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

4 Data Requirements for the Registration Re view of Zinc Chloride (PC Code 087801)

Guideline
Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI receipt)
850.3300 or
OECD 209 1,2,3 Activated Sludge Respiration Inhibition TGAI 12

835.1230 1 Sediment and soil adsorption/desorption TGAI 12

850.4400 1,2,3,4 Aquatic plant growth using floating macrophyte Lemna gibba TGAI 12

850.4500 1,2,4,5 Aquatic Plant Growth (green alga, freshwater diatom, saltwater diatom) TGAI 12

850.4550 1,2,4,6 Aquatic Plant Growth (cyanobacteria) TGAI 12

1 Study is required to support the registration review of wood preservative uses, material preservative uses, and
outdoor moss control uses.

2 Analytical measurements of zinc (total, dissolved, an d free) and the following water quality parameters that are critical to metal speciation in solution are required: temper ature, pH, dissolved organic carbon (distribution of humic and fulvic acids), major cation (Ca, Mg, Na and K), major anions (SO 4 and Cl), alkalinity, and sulfide content.

3 Because applied zinc and zinc salts will react in aqueous solutions to form free zinc ion and dissolved complexes, the Agency recognizes there is potential for tests conducted with one zinc active ingredient to potentially bridge to another. However, the Agency also recognizes that the content and formation of the free zinc ion and complexes in a test can be affected by dissolution and reaction kinetics and therefore data generated for on e of the more soluble zinc active ingredient forms is recommended for use in such bridging.

4 Results from a tier II study are required to be submitted to satisfy this requirement.

5 Results for three species ( Selenastrum capricornutum (green alga), one freshwate r diatom, and one saltwater diatom) are required to fulfill requirement. If the NOAE C of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

6 Results for one species of cyanobacteria are required to fu lfill requirement. If the NOAEC of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

5 Data Requirements for the Registration Review of Zinc Sulfate (PC Code 089001)

Guideline
Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI receipt)
850.3300 or
OECD 209 1,2,3 Activated Sludge Respiration Inhibition TGAI 12

835.1230 1 Sediment and soil adsorption/desorption TGAI 12

850.4400 1,2,3,4 Aquatic plant growth using floating macrophyte Lemna gibba TGAI 12

850.4500 1,2,4,5 Aquatic Plant Growth (green alga, freshwater diatom, saltwater diatom) TGAI 12

850.4550 1,2,4,6 Aquatic Plant Growth (cyanobacteria) TGAI 12

1 Study is required to support the registration review of wood preservative uses, material preservative uses, and
outdoor moss control uses.

2 Analytical measurements of zinc (total, dissolved, an d free) and the following water quality parameters that are critical to metal speciation in solution are required: temper ature, pH, dissolved organic carbon (distribution of humic and fulvic acids), major cation (Ca, Mg, Na and K), major anions (SO 4 and Cl), alkalinity, and sulfide content.

3 Because applied zinc and zinc salts will react in aqueous solutions to form free zinc ion and dissolved complexes, the Agency recognizes there is potential for tests conducted with one zinc active ingredient to potentially bridge to another. However, the Agency also recognizes that the content and formation of the free zinc ion and complexes in a test can be affected by dissolution and reaction kinetics and therefore data generated for on e of the more soluble zinc active ingredient forms is recommended for use in such bridging.

4 Results from a tier II study are required to be submitted to satisfy this requirement.

5 Results for three species ( Selenastrum capricornutum (green alga), one freshwate r diatom, and one saltwater diatom) are required to fulfill requirement. If the NOAE C of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

6 Results for one species of cyanobacteria are required to fu lfill requirement. If the NOAEC of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

6 Data Requirements for the Registration Review of Zinc (PC Code 129015)

Guideline
Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI receipt)
850.3300 or
OECD 209 1,2,3 Activated Sludge Respiration Inhibition TGAI 12

835.1230 1 Sediment and soil adsorption/desorption TGAI 12

850.4400 1,2,3,4 Aquatic plant growth using floating macrophyte Lemna gibba TGAI 12

850.4500 1,2,4,5 Aquatic Plant Growth (green alga, freshwater diatom, saltwater diatom) TGAI 12

850.4550 1,2,4,6 Aquatic Plant Growth (cyanobacteria) TGAI 12

1 Study is required to support the registration review of wood preservative uses, material preservative uses, and
outdoor moss control uses.

2 Analytical measurements of zinc (total, dissolved, an d free) and the following water quality parameters that are critical to metal speciation in solution are required: temper ature, pH, dissolved organic carbon (distribution of humic and fulvic acids), major cation (Ca, Mg, Na and K), major anions (SO 4 and Cl), alkalinity, and sulfide content.

3 Because applied zinc and zinc salts will react in aqueous solutions to form free zinc ion and dissolved complexes, the Agency recognizes there is potential for tests conducted with one zinc active ingredient to potentially bridge to another. However, the Agency also recognizes that the content and formation of the free zinc ion and complexes in a test can be affected by dissolution and reaction kinetics and therefore data generated for on e of the more soluble zinc active ingredient forms is recommended for use in such bridging.

4 Results from a tier II study are required to be submitted to satisfy this requirement.

5 Results for three species ( Selenastrum capricornutum (green alga), one freshwate r diatom, and one saltwater diatom) are required to fulfill requirement. If the NOAE C of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

6 Results for one species of cyanobacteria are required to fu lfill requirement. If the NOAEC of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.Docket Number: EPA-HQ-OPP-2009-0011 www.regulations.gov

7 Data Requirements for the Registration Revi ew of Zinc Sulfate Monohydrate (PC Code 527200)

Guideline
Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI receipt)
850.3300 or
OECD 209 1,2,3 Activated Sludge Respiration Inhibition TGAI 12

835.1230 1 Sediment and soil adsorption/desorption TGAI 12

850.4400 1,2,3,4 Aquatic plant growth using floating macrophyte Lemna gibba TGAI 12

850.4500 1,2,4,5 Aquatic Plant Growth (green alga, freshwater diatom, saltwater diatom) TGAI 12

850.4550 1,2,4,6 Aquatic Plant Growth (cyanobacteria) TGAI 12

1 Study is required to support the registration review of wood preservative uses, material preservative uses, and
outdoor moss control uses.

2 Analytical measurements of zinc (total, dissolved, an d free) and the following water quality parameters that are critical to metal speciation in solution are required: temper ature, pH, dissolved organic carbon (distribution of humic and fulvic acids), major cation (Ca, Mg, Na and K), major anions (SO 4 and Cl), alkalinity, and sulfide content.

3 Because applied zinc and zinc salts will react in aqueous solutions to form free zinc ion and dissolved complexes, the Agency recognizes there is potential for tests conducted with one zinc active ingredient to potentially bridge to another. However, the Agency also recognizes that the content and formation of the free zinc ion and complexes in a test can be affected by dissolution and reaction kinetics and therefore data generated for on e of the more soluble zinc active ingredient forms is recommended for use in such bridging.

4 Results from a tier II study are required to be submitted to satisfy this requirement.

5 Results for three species ( Selenastrum capricornutum (green alga), one freshwate r diatom, and one saltwater diatom) are required to fulfill requirement. If the NOAE C of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.

6 Results for one species of cyanobacteria are required to fu lfill requirement. If the NOAEC of the green alga is > 1 ppm zinc, the Agency may consider waiving data for other algal species.Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

United States Prevention, Pesticides September 2009 Environmental Protection and Toxic Substances Agency (7510P)



# Zinc, Zinc Salts and Zeolites Final Work Plan Registration Review September 2009Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review



### TABLE OF CONTENTS

Zinc, Zinc Salts and Zeolites Regi stration Review Team Members................... 1
I. Introduction.................................................................................... 2 II. Comments on Preliminary Work Plan ................................................ 2 III. Risk Assessment and Data Needs ...................................................... 6 IV. Timeline ..................................................................................... 14 V. Glossary of Terms & Abbreviations .................................................... 15Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

Zinc, Zinc Salts and Zeolites Registration Review Team

Human Health & Environmental Effects
Nathan Mottl
Srinivas Gowda

Risk Management Eliza Blair Lance Wormell

Office of General Counsel Philip Ross

1Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

I. Introduction:

This is EPA’s Final Work Plan for the re gistration review of zinc, zinc salts and zeolites. The work plan includes the expect ed registration review timeline. The work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document which was posted in th e zinc, zinc salts a nd zeolites registration review docket, and any other comments c oncerning the initial docket postings. The Summary Document provided information on what EPA knows about the pesticide and what additional risk analyses and data or in formation the Agency believes are needed to make a registration review decision.

The Agency has begun to implement the new Registration Review program pursuant to FIFRA Section 3(g) and intends to review each registered pesticide approximately every 15 years to determine whether it continues to meet the FIFRA standard for registration. The public phase of registration revi ew begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state clearly what it knows about the pesticide and what additional risk analyses and data or
information it believes are needed to make a registration review decision.

The Zinc, Zinc Salts and Zeolites Prel iminary Work Plan was published in the federal docket on March 25, 2009. An amen dment that included updated water-body impairment information was published in the federal docket on March 31, 2009. The 90- day comment period ended on June 23 rd , 2009. The Preliminary Work Plan document is
available on www.regulations.gov , docket number EPA-HQ-OPP-2009-0011.

II. Summary of Comments Receive d on Preliminary Work Plan:

EPA received one whitepaper containing several separate comments during the public comment period on the initial docket, desc ribed below. The data needs, work plan and timeline described in the Preliminary Work Plan remain as they were presented initially. This document makes final the work plan for the zinc, zinc salts and zeolites registration review process.

Comment: The Agency has sufficient information to fully evaluate the potential risks of exposure to zinc or silver zeolites and should revise its registration review work plan accordingly.

Response: As cited on page 7 and 8 of “Summa ry of Human Health Effects Data for Zinc, Zinc Salts and Zeolites Registra tion Review Document”, dated March 4, 2009:

The silver-zinc zeolites labels are unique from the rest of the zinc salt active ingredients because they are used for indire ct food contact uses (countertops, appliances, kitchen hardware, tiles, food trays, food processing equipment, food storage containers, food packaging, food processing utensils). Becaus e of the unique chem istry of the silverzinc zeolites and the fact that these products are used for indirect food uses, additional silver-zinc toxicity data are need ed for a dietary assessment.

2Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

According to EPA’s review 1 “the registrant must subm it or cite valid toxicology studies conducted with the end use formula sil ver-zinc product for sub-chronic toxicity in the rode, sub-chronic toxicity in the non-rode nt, developmental toxicity in the rodent, and reproductive toxicity in the rodent. Separate to xicity studies with t echnical grade silver and technical grade zinc are not required, but toxicity data on the formula with the highest percentage of silver and zinc should be conducted. This will support other enduse formulations from the regi strant containing lowe r percentages of silver and zinc.”

In reviewing silver and zinc contai ning compounds, AD decided that zeolites compounds may have their own toxicological pa ttern and zeolite-based silver-zinc active ingredients were not similar to salts of silver and hazards would need to be considered separately. 2,3

In summary, during registration of the silver-zinc zeolite products, the Agency had previously determined that the zeolites are unique chemically and toxicologically from the other silver and zinc products. The EPA concluded that chemically, zeolitebased silver active ingredients were not simila r to salts of silver and zinc and hazards would need to be considered separately.

In registration review, EPA will examin e the hazard databases for the silver-zinc zeolites and attempt to determine whether change s in science policy or deficiencies in the databases materially affected the overall risk picture. During the l iterature search the Agency identified the data gaps in the silv er-zinc zeolite toxicol ogy database based on the review of the existing Agency records. The data gaps are presented in Section III of
this document.

The Agency could not conduct a dietar y review because the proper toxicity
information was not available as per an earlier Agency review

. In addition to this review, other silver zeolite decision documents were referenced to pr ovide context on the Agency’s position on toxicity data require ments as far as Silver and Silver-Zinc
Zeolites. 2,3

Comment: 90-day dermal toxicity in rodents - It is possible to conclude that zeolites are not expected to resu lt in systemic toxicity from the dermal route of exposure. Based on their poor water solubility and ioni c characteristics, th ese compounds are not expected to cross the intact skin barrier and dermal uptake is negligible. Even in the case of damaged skin, uptake is expected to be ne gligible because of poor water solubility and their ionic nature (Fruijtie r-Polloth (2009) HERA (2004)).

Response: The Agency will review the source s [(Fruijtier-Polloth (2009) and HERA (2004)] during the registra tion review process to determine whether a waiver is in order. To date, the Agency is not aware of a 90-day dermal toxicity study that has been submitted or identified in the existing literature for silver-zinc zeolites and can not draw any conclusions on whether dermal absorption is negligible.

Comment: 90-day oral, developmental, reproductive studies - Since the Agency failed to provide a clear explanat ion for its request for more data, publicly

3Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

available information on the reported effects fr om silver and/or silver/zinc zeolite-type products was reviewed to determine whether sufficiently different effects from those expected from either the active ingredient or the inert component could be identified.

The registrant referenced publicly availa ble EPA reviews of data submitted to EPA, and noted that it is ex tremely difficult to clearly identify from the EPA reviews exactly what comprised the test material, ev en in terms of the metal components of the zeolite. If other components were present in the test material, the potential effects associated with those components cannot be identified. The regist rant concluded from these publicly-available reviews that no suffi ciently different eff ects were found, and no further toxicity data should be need ed to complete Registration Review.

Response: The Agency has determined that there is a potential for dietary exposure in the registration review and provi ded context and refere nces to support its position. The purpose of this registration re view scoping document was to determine whether sufficient data are available to suppor t registration review. Based on researching existing Agency reviews to date on the silv er-zinc zeolites, this registration review concluded more toxicity data is needed for silver-zinc zeo lites. This decision reflects previous Agency decisions and documents on file. The Agency has a limited toxicity database of existing literature and registrant submitted studies for silver-zinc zeolites and the Agency encourages submission of studies. The Agency has appreciated the feedback on the Preliminary Work Plan and the inform ation provided by the registrant during the public comment period and anticipates further discussions at a later time. The EPA will review the public comment period submissions and will decide whether any of this data presented in the submission will affect the anticipated toxicity data needs.

According to registration records, th e Agency had required toxicity data for silver-zinc zeolites in the past. In fact, the existing silver-zinc zeolite existing labels (EPA Reg 40810-12, 40810-24, etc.) express toxicity data needs and stipulate only timelimited approvals to support the indirect f ood uses. The registrant pointed out some toxicity information on inert zeolite, silver, zi nc, silver copper zeolite s, and silver zeolites in their response submissions. However, the re gistrant did not cite many specific toxicity studies of silver zinc zeolites and the Agen cy can not draw any meaningful comparisons or conclusion based on limited information. The Agency needs specific silver-zinc zeolite toxicity data to make meaningful c onclusions on the differing toxicity of silverzinc zeolites from other silver zeolites, and/or silver, and zinc ions, etc. to see if the toxicity is comparable or not. At this time th e EPA has taken the posi tion that toxicity of
silver salts and silver zeolites are not comparable and in the review of Irgaguard B5000, the Agency were not able to resolv e the existing toxi city data needs. 2,3 In the past for silver zeolites, the Agency has concluded that silver zeolite was not similar to salts of
silver. 2 There is uncertainty on how the additi on of different proporti ons of silver and
zinc ions in different zeolite carriers would influence the dose related toxicity in different target organs.

Comment: Documentation has been submitted to FDA (as well as to EPA) that provides evidence that the IEC component of the Irgaguard products remain within the

4Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

preserved materials. These studies were conducted to support FDA Effective Food Contact Notifications (FCN#193, #248, #275, #294) for the Irgaguard products as components of polymers used in food pack aging and other food contact surfaces as regulated by FDA under FFDCA Section 409. Fo r each of the three Irgaguard products, Ciba conducted worst-case migration studi es following FDA guidance to determine potential movement out of a preserved articl e into food that contacts the surface of the article. In accordance with FDA guidance, th e Irgaguard product wa s incorporated into Low Density Polyethylene (LDPE), which is cons idered to be a worst-case scenario. The maximum use rate of the Irgaguard product was used (3% w/w of the polymer). Small plaques (1 x 4 inch) of the LDPE were then subjected to severe c onditions to determine migration of components out of the LDPE into a food simulant. The severe conditions included large surface area to volume ratio, e xposure to an extremely aggressive food simulating solvent (10% ethanol with 1% sodi um chloride), exposure for up to 10 days at
40 o C with a 2 hour preheat at 100 o C. The 1% sodium chloride solution was added to the standard FDA solvent (10% ethanol) because use of the ethanol alone resulted in no detectable levels of any of the potenti al migrating compounds. Ciba conducted preliminary work with the standard FDA solv ents (10% and 95% ethanol). There were no detectable levels of silver using either st andard solvent. The a ddition of a 1% NaCl solution was found to increase the ionic strength of the extractants, resulting in low but
detectable levels of silver. The sodium fr om the sodium chloride is preferentially exchanged with silver and zinc on the surface of the LDPE wafer and to ensure maximum solubility of the inorgani c silver and zinc ions.

Response: The Agency currently has one s ilver-zinc migration study (MRID 46174701):

Viczkus, J. (2003) Migration Study From Low Density Polyethylene (LDPE) Into 10% Ethanol With 1% Sodium Chloride: Irgaguard B7000. Project Number: FDA2002N04, B7000. Unpublished study prepared by Ciba Speciality Chemicals Corp. 71 p.

This study will be reviewed for acceptab ility during registration review. Thank you for bringing this information to our attentio n. If there are more silver-zinc migration studies, we would encourage submission of these documents as well.

Comment: There is no evidence of developmen tal toxicity in studies conducted by Kanebo with a silver-zin c zeolite comparable to Irgaguard B5000 (MRID 41638502, 42245403, 42653201, 42845701).

Response: The Agency will be reviewing the studies submitted by Kanebo (41638502, 42245403, 42653201, 42845701) for acceptability with GLN 870.3700 during registration review.

References

1 Irgaguard B5000: Request for assessment of ri sk from proposed food contact uses of the active ingredient. Memorandum from T. McMahon, PhD to Dennis Edwards/Marshall Swindell/Tony Kish, U.S.EPA/AD. March 6, 2003.

5Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

2 U.S. EPA 2004a. Memorandum from J. Che n, PhD. to Norm Cook. Subject: Interim Position for Toxicological End- points for Silver. P.C. Code: 309200.

3 U.S. EPA 2004b. Memorandum for T. McMa hon to T. Kish/M.Swindell. Silver
- Report of the Antimicrobials Division T oxicity Endpoint Committee (ADTC). October 20, 2004.

In addition to addressing the comments above, EPA has also included amended water body impairment information in this Fina l Work Plan. Please see “Revised Zinc, Zinc Salts and Zeolites Summary Document: Registration Review Pr eliminary Work Plan Addendum”, dated March 31, 2009, for additional information.

In the Preliminary Work Plan, the Agen cy solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were received during the comment period concerning these issues.

III. Risk Assessment and Data Needs:

A Reregistration Eligibility Decision (RED) was completed for elemental zinc in 1992. However, to complete registration revi ew, additional data are needed to conduct
the human health and ecol ogical risk assessments.

Human Health Risk

Note : Several existing registrations exist fo r silver-zinc and zinc zeolites which are composed of zinc (elemental) (PC Code 129015). Zeolites are clay -like materials that
can be combined with various metal ions . According to MRID 458033-01, “the silverzinc zeolites are silver-zinc ion-exchange products which are stabilized by an inert ion exchange carrier.” The silver-zin c zeolites labels are unique fr om the rest of the zinc salt active ingredients because they are used for indirect food contact uses (countertops, appliances, kitchen hardware, tiles, food tray s, food processing equipment, food storage containers, food packaging, food processing ut ensils); drinking water contact uses (tubing, plumbing supplies and fixtures); derm al contact (apparel items and interior furnishings) and HVAC uses. The other zinc sa lts are not used for food contact products. There are currently no tolerances or exemptions for the requirement of a tolerance for any zinc salts in this registrati on review case. A tolerance or exemption from the requirement of tolerance may be needed for zinc portion of silver-zinc zeolites for these indirect food

uses.

Acute Toxicity

Zinc Chloride

Data from the existing RED indicates that zinc chloride has an acute toxicity category II for acute oral (rat). It is a corrosi ve for the skin and eyes (acute toxicity

6Docket Number: EPA-HQ-OPP-2009-0011 Final Work Plan www.regulations.gov Registration Review

category I). The acute inhalation study for zi nc chloride is assigned as acute toxicity category III.

Zinc Oxide

Data from the existing RED indicates th at zinc oxide has an acute toxicity category IV for acute oral (rat). It is a not a skin irritant ( acute toxicity category IV) and only a mild eye irritant (acute toxicity category III). The acute inhalation studies were waived for the technical active ingredient.

Zinc Sulfate Monohydrate

Data from the existing RED indicates that zinc sulfate monohydrate has an acute toxicity category III for acute oral (rat). It is a mild eye irritant (acute toxicity category III). The acute inhalation, dermal and skin sensitization studies were waived for the technical active ingredient.

Zinc (Elemental)

Data for zinc (elemental) was not ava ilable from the existing RED. However, data from a product toxicity re view containing 1.36% zinc indicates that zinc (elemental) has an acute toxicity category IV for acute or al, acute dermal and acute inhalation. It is a mild skin irritant (acute toxicity category IV) and mild eye irrita nt (acute toxicity category III) and a nonsensitizer.

Subchronic and Chronic Toxicity

The Food and Drug Administration (FDA) c onsiders zinc chloride as generally recognized as safe (GRAS) for use in foods and nutrients under 21 CFR 182.8985 and 21
CFR 182.5991. The FDA also considers zinc oxide and zinc sulfate as GRAS for use in foods under 21 CFR 182.8991 and 182.8997, respectively. The FDA also considers zinc
oxide and zinc sulfate as GRAS for use in nutrients under 21 CFR 182.5985 and 182.5997, respectively.

Zinc is ubiquitous in the environment and o ccurs in the earth’s crust at an average concentration of approximately 70 mg/kg. This ion exists in the form of zinc salts such as zinc sulfide, zinc carbonate , and zinc oxide. Zinc is also an essential nutrient in the body. For toxicological concer ns, there are adequate toxi cology studies in the zinc
database to evaluate incidental oral exposures. At high leve ls, oral exposure to zinc in animal studies may result in toxic effects such as pancreatic and re nal lesions as well as histological alterations in the pituitary and adrenal glands. In general, the levels of zinc causing these toxicological effects occur at much higher dose levels than the level
recommended for nutritional use and th at is naturally available in food. Zinc is widely distributed in plants and animals, and is nor mally present in food. Zinc is also a normal part of metabolism in all living organisms

. Based on this information, no toxicological endpoints were selected.

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However, the silver-zinc zeolites labels ar e unique from the rest of the zinc and zinc salts active ingredients because they are used for indirect food contact uses (countertops, appliances, kitchen hardware, ti les, food trays, food processing equipment, food storage containers, food packaging, food processing utensils). Because of the unique chemistry of the silver-zinc zeolites a nd the fact that these products are used for indirect food uses, additional silver-zinc toxicity data are needed for a dietary assessment.

According to the Agency’s review, “the registrant must submit or cite valid toxicology studies conducted w ith the end use formula silver-zinc product for subchronic toxicity in the rodent, subchronic toxicity in the non-rodent, developmental toxicity in the rodent, and reproductive toxicity in the rodent. Separate toxi city studies with technical grade silver and technical grade zinc are not required, but toxicity data on the formula with the highest percentage of silver and zinc should be conducted. This will support other end-use formulations from the registrant containing lower percentages of silver and
zinc.”

In reviewing silver and zinc contai ning compounds, the Agency has suggested that zeolites compounds may have their own to xicological pattern. Zeolite-based silverzinc active ingredients are not similar to salts of silver and zinc, and hazards would need to be considered separately fo r each silver-zinc zeolite compound.

Dietary and Drinking Water Exposure

The Food and Drug Administration (FDA) c onsiders zinc and zinc chloride as generally recognized as safe (GRAS) fo r use in foods and nutrients under 21 CFR
182.8985 and 21 CFR 182.5991. The FDA also consid ers zinc oxide and zinc sulfate as GRAS for use in foods under 21 CFR 182.8991 and 182.8997, respectively. Due to low toxicity concerns, EPA will not conduct a dietar y risk assessment for zinc and zinc salts.
EPA believes that zinc and zinc salts are not a concern at th e current registered levels
which are similar to those occurring naturally in food.

It should be noted, however, that there are several end-use silver-zinc zeolite registrations that have dietary and drinking water uses. The Agency will be reviewing silver and other related compounds (e.g. silver -zinc zeolites) on a case-by-case basis to determine whether the compound is similar to an existing class (e.g., s ilver salts, silverzinc zeolites). For dietary exposure for silver -zinc compounds, the registrant must submit or cite valid toxicology studi es conducted with the end- use silver-zinc product for subchronic toxicity in the r odent, subchronic toxicity in the non-rodent, developmental toxicity in the rodent, and reproductive toxicity in the rodent. Sepa rate toxicity studies with technical grade silver and technical grad e zinc are not required, but toxicity data on the formula with the highest percentage of silver and zinc should be conducted. This will support other end use formulations from the re gistrant containing lower percentages of silver and zinc. Once the Agency, receives th e appropriate toxicity data, the Agency will need to conduct a dietary assessment for silver-zinc zeolite.

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Occupational and Residential Exposure

For zinc and zinc salts there are currently 15 registered labels . Most of the uses include handler exposure to mixing/loading soluble concentrates a nd wettable powders during manufacturing of materi al preservatives and wood pressure treatment exposures to zinc from ammonical copper zinc arsenate (ACZA). There w ould also likely be dermal and inhalation exposure applying zinc pres ervative sprays to moss on walkways and roofs. Occupational postappl ication exposure scenarios would include dermal and incidental ingestion from contact with wood products (u tility poles, building poles, foundation piling, marine piling, etc.) and re sidential postapplication exposures would
include dermal and incidental ingestion to treated counter tops and treated apparel and pressure treated decks.

As mentioned in the toxicology section (s ection 2), zinc is ubiquitous in the
environment and occurs in the earth’s crust at an average concentration of approximately 70 mg/kg. Zinc is also an essential nutrien t in the body and is GRAS in food as dietary supplements. At registered application rates, exposure to zinc salt pe sticides is not likely to be higher than that which is found in ambi ent levels and at leve ls of zinc nutrient which are required by the human body.

For silver-zinc and zinc zeolites, the Agency may n eed to conduct occupational and/or residential exposure assessments, partic ularly from dermal contact, to treated apparel and incidental exposure vi a mouthing to treated fabrics.

Aggregate and Cumulative Exposure

In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to pesticide residues in food and drinking water, and non-occupationa l pesticide exposures. The Food and Drug Administration (FDA) considers zinc and salts as GRAS for use in foods. EPA believes zinc and salts are of low toxicity and EPA does not intend to develop aggregate exposure assessments
for zinc and zinc salts to determine if cer tain use patterns pose any risk based on the calculated aggregate exposures. However, for silver-zinc zeolites, an aggregate assessment may be needed. At this time, EP A has not yet determined whether zinc and
salts have a common mechanism with ot her compounds; consequently, a cumulative assessment will not be performed for either of these chemicals.

Anticipated Human Health Data Needs

In reviewing silver- and zinc-containi ng compounds, AD determined that zeolite compounds may have their own toxicological pa ttern and zeolite-base d silver-zinc active ingredients were not similar to salts of silv er and zinc and hazards would need to be considered separately for each silver-zinc zeolite compound. Therefore, for the purposes of registration review, toxicity data needs for the silver-zinc and zinc zeolites are as
follows:

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Human Health Toxicity Data Needs:

• (GLN 870.3100) 90-Day Or al Toxicity-rodent

• (GLN 870.3150) 90-Day Oral Toxicity-non-rodent

• (GLN 870.3250) 90-Day Dermal Toxicity-rodent

• (GLN 870.3700) Developmental Toxicity- rodent

• (GLN 870.3800) Reproductive Toxicity- rodent

Once the Agency receives and reviews these toxicological studies, additional occupational, dietary and aggregate assessments may be needed. Further information is available in “Summary of Hu man Health Effects Data fo r the Zinc, Zinc Salts and Zeolites Registration Review Deci sion Document” dated March 4, 2009.

Anticipated Physical/ Chemic al Property Data Needs

All product chemistry data requirements ha ve been fulfilled for zinc, zinc salts and zeolites. Therefore, no additional phys ical/chemical property data are needed.
Further information is available in “Summa ry of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Zinc Salts Re gistration Review Summary Document”, dated March 31, 2009.

Ecological Risk

The metal zinc has been identified as a cause of impairment for water bodies listed as impaired under sect ion 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attain s_nation_cy.cause_detail_303d?p_cause_grou p_id=706 . This list indicates 437 impair ments listed for zinc in water and 10 for zinc in sediment. The Agency will determine whether pesticide use was a contributor and/or determine if use might occur in these watersheds.

Environmental fate and ecological risk assessments have not been conducted for the active ingredients in this case. The Agency anticipates conducting environmental fate and ecological risk assessments for outdoor re sidential uses for cont rol of moss on roofs, decks, steps, patios, walks, bricks, cement, sidewalks, fences, fence posts, foundations
and other outdoor structures made of co mposition shingles, wood, gravel, brick and unpainted cement.

Since most of the applied zinc salts will transform to zinc oxide/hydroxide, the ecological effects and environmental fate data requirements for zinc oxide are sufficient for the other active ingredients. For zinc ch loride, the Agency anticipates needing some or all of, the ecological effects and environmen tal fate data requirements listed for zinc
oxide in order to conduct the environmenta l fate and ecological risk assessments, including an endangere d species assessment.

The Agency has not conducted a risk assessment that supports a complete endangered species determination. The eco logical risk assessment planned during

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registration review will allow the Agency to determine whether zinc, zinc salts and zeolites’ use has “no effect” or “may affect ” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

Anticipated Environmental Fate and Ecological Data Needs

The Agency anticipates needing the followi ng data in order to conduct a complete environmental fate and ecotoxicity asse ssment, including an endangered species
assessment for all uses:

Environmental Fate Risk Assessment Data Needs :

• (GLN 850.6800) modified activated sl udge respiration inhibition; and

• (GLN 835.1110) activated sl udge sorption isotherm

Ecological Risk Assessment Data Needs :

• (GLNs 850.4400 & 850.5400) algal toxicity (Tie r II) using freshwater green alga, Selenastrum capricornutum.

Potential Zinc Oxide Ecological Effects a nd Environmental Fate Data for Outdoor Wood Preservative Uses

If zinc oxide is intended for treatment of wood products used in outdoor scenarios (e.g., decks, decking materials, aquatic uses), the Agency anticipates needing some, or all of, the following data in order to conduct the environmental fate and ecological risk assessments, including an endangered species as sessment. However, note that which data are required will depend on: the quantities of zinc oxide (and/or major degradates or metabolites) leaching from wood; the type s of chemical(s) leaching from wood (e.g., parent compound, major degradates or metabo lites); the outdoor use scenarios in which zinc oxide-treated wood may be used; and th e Agency's evaluation of the leaching data along with the available use, effects, a nd exposure information for zinc oxide:

Ecological Effects Studies :

To support registration of wood preserva tives, the following ecological effects and environmental data are required.

a. Required (R) Ecological Effects Data :

Guideline Description of Data Requirement
Number

850.1010: Aquatic invertebrate acute EC 50 using Daphnia magna (using TGAI and TEP) (satisfied);

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850.1075: Fish acute LC 50 s with a coldwater (rainbow trout, preferred) and a warmwater (bluegill sunfish, preferre d) species (using TGAI and Typical End-Use Product (TEP) (satisfied);
850.2100: Avian acute oral LD 50 with bobwhite quail (preferred) or mallard duck (using Technical Grade Active In gredient (TGAI) (satisfied); 850.4225: Seedling emergence - do se response using rice ( Oryza sativa ); 850.4250: Vegetative vigor - dose response using rice ( Oryza sativa ); 850.4400: Aquatic plant growth using floating macrophyte Lemna gibba; and 850.5400: Aquatic plant growth (algal and aq uatic plant toxicity ) - Tier II (dose response) (using TGAI or TEP) – Four species: freshwater green alga, Selenastrum capricornutum , blue-green cyanobacterium, Anabaena flosaquae, the freshwater diatom, Navicula pelliculosa, and marine diatom,
Skeletonema costatum

.

b. Conditionally-Required ( CR) Ecological Effects Data:

850.1025: Oyster acute (shell deposition) or 850.1055: Acute oyster embryo larval

850.1035: Acute Mysid
850.1045: Acute Penaeid

850.1075: Acute Fish Toxicity (est uarine/marine species) Acute LC 50 s/EC 50 s using estuarine/marine organisms (fish) species (using TGAI and TEP); 850.1300: Aquatic Invertebrate life cycle study (using most sensitive species -
freshwater or estuarine/marine ) Daphnid chronic toxicity test; 850.1350: Aquatic Invertebrate life cycle study (using most sensitive species - freshwater or estuarine/marine) Mysid chronic toxicity test; 850.1400: Fish early-life stage toxicity studies (using TGAI and most sensitive species - freshwater or estuarine/marine); 850.1500: Fish (freshwater and/or estuarine/ marine species) life cycle study (using TGAI);

850.1710: Oyster BCF
850.1730: Fish BCF 850.1850: Aquatic organism bioavailability/b iomagnifications, toxicity tests (using TGAI or PAIRA);

850.1735: Whole sediment, acute inverteb rates (freshwater) (using TGAI); 850.1740: Whole sediment; acute invertebrate s (estuarine/marine) (using TGAI); 850.1950: Field testing for aquatic organi sms (estuarine/marine) (using TEP); 850.2200: Avian dietary LC 50 with bobwhite quail and/or mallard duck (using TGAI) (satisfied); 850.2300: Avian reproductive studies with bobwhite quail and/or mallard duck (using TGAI); and

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None: Whole sediment - chronic invertebrates (freshwater and/or estuarine/marine) (using TGAI or TEP). 850.3020: Honeybee acute contact LD 50 (using TGAI); 850.3030: Toxicity of residues to honeybees , “Honey Bee Toxicity of Residues on Foliage” (using TGAI); 850.4300: Terrestrial Plants Field Study (using TGAI); 850.4450: Aquatic Plants Field Study (using TGAI)

c. Required Environmental Fate Data :

Guideline Description of Data Requirement
Number

835.2240: Photodegradation in wate r (using TGAI or PAIRA); 835.2240: Photodegradation in soil (using TGAI or PAIRA); 835.1230/ Leaching and/ 835.1240: Adsorption/Desorption studies (using TGAI or PAIRA); 835.4100: Aerobic soil metabolism (using TGAI or PAIRA); None: Aquatic leaching from wood study. (For guidance refer to: Standard Method of Determining The Leachab ility of Wood Preservatives,
American Wood-Preservers’ A ssociation Standard E11-06); None: Soil leaching from wood study (AWPA E20-04)

835.4400: Anaerobic aquatic metabolism (using TGAI or PAIRA); and 850.6800: Modified activated sludge, re spiration inhibition (using TGAI).

d. Conditionally-Required (CR) Environmental Fate Data :

835.4200: Anaerobic soil metabolism (using TGAI or PAIRA); 835.4300: Aerobic aquatic metabolism (using TGAI or PAIRA); 835.4400: Anaerobic aquatic metabolism (using TGAI or PAIRA); 835.6200: Aquatic (sediment) [using Typi cal End-use Product (TEP)]; and None: Monitoring of representative U. S. waters (residue of concern).

The above listed data requirements fo r zinc oxide will also satisfy data requirements for residential outdoor moss contro l uses of zinc chloride, zinc sulfate monohydrate, and zinc metal.

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IV. Timeline:

EPA has created the following estimated timeline for the completion of the zinc,
zinc salts and zeolite s registration review.



### Registration Review for Zi nc, Zinc Salts and Zeolites Projected Registration Review Timeline

Activities Time

Opening Docket Open Docket Completed March 2009

Close Public Comment Period Completed June 2009 Case Development

Final Work Plan September 2009

Issue DCI June 2010

Data Submission June 2011 Preliminary Risk Assessment June 2013

Close Public Comment Period September 2013
Registration Review Decision Proposed Registration Review Decision December 2013

Public Comment Period March 2013 Final Registration Review Decision & Begin Post-Decision Follow-up 2013 Total (years) 4

Next Steps:

A Data Call-In (DCI) will be developed regarding the data gaps listed under the
“Risk Assessment and Data Needs” sec tion. Also, human health and ecological
assessments will be conducted for all uses.

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V. GLOSSARY of TERMS & ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue ASTM American Society for Testing and Materials
AWPA American Wood Preserver’s Association
CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals
DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration
EEC Estimated Environmental Concentration EPA Environmental Protection Agency
EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model
IR Index Reservoir
LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.
LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LOC Level of Concern
LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure
MRID Master Record Identifi cation (number). EPA's system of recording and tracking
submitted studies. MUP Manufacturing-Use Product
NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System
NR Not Required
NOAEL No Observed Adverse Effect Level
OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area

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16 PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval ppb Parts Per Billion
PPE Personal Protective Equipment

ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer
Risk Model RAC Raw Agriculture Commodity RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose RQ Risk Quotient SCI-GROW Tier I Ground Water Computer Model
SAP Science Advisory Panel SF Safety Factor
SLN Special Local Need (Registrati ons Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient
TEP Typical End-Use Product USDA United States Department of Agriculture UF Uncertainty Factor WPS Worker Protection Standard